A Neuron-Specific Gene Therapy Relieves Motor Deficits in Pompe Disease Mice

作者：Lee Ni Chung; Hwu Wuh Liang; Muramatsu Shin Ichi; Falk Darin J; Byrne Barry J; Cheng Chia Hao; Shih Nien Chu; Chang Kai Ling; Tsai Li Kai; Chien Yin Hsiu^*

来源：Molecular Neurobiology, 2018, 55(6): 5299-5309.

DOI：10.1007/s12035-017-0763-4

• Pompe disease
• Glycogen
• Gene therapy
• Adeno-associated viral vector
• Neuron-specific
• Enzyme replacement therapy

In Pompe disease, deficient lysosomal acid alpha-glucosidase (GAA) activity causes glycogen accumulation in the muscles, which leads to weakness, cardiomyopathy, and respiratory failure. Although glycogen accumulation also occurs in the nervous system, the burden of neurological deficits in Pompe disease remains obscure. In this study, a neuron-specific gene therapy was administered to Pompe mice through intracerebroventricular injection of a viral vector carrying a neuron-specific promoter. The results revealed that gene therapy increased GAA activity and decreased glycogen content in the brain and spinal cord but not in the muscles of Pompe mice. Gene therapy only slightly increased the muscle strength of Pompe mice but substantially improved their performance on the rotarod, a test measuring motor coordination. Gene therapy also decreased astrogliosis and increased myelination in the brain and spinal cord of Pompe mice. Therefore, a neuron-specific treatment improved the motor coordination of Pompe mice by lowering glycogen accumulation, decreasing astrogliosis, and increasing myelination. These findings indicate that neurological deficits are responsible for a significant burden in Pompe disease.

• 出版日期2018-6